[Show abstract][Hide abstract] ABSTRACT: In a hospital based case-control study of pancreatic cancer in Ontario and Quebec, a total of 174 incident pancreatic cancer cases and 136 healthy controls were compared for their family history of cancer. Information regarding the ages and sites of cancer was taken for 966 first-degree relatives of the cancer cases and for 903 first-degree relatives of the controls. A total of 150 cancer cases were reported among the relatives of the cases, compared to 122 cases among the relatives of the controls (relative risk 1.15; p = 0.23). Pancreatic cancer was the only site statistically in excess in the case relatives, compared to the control relatives (relative risk = 5.0; p = 0.01). The lifetime risk of pancreatic cancer was 4.7% for the first-degree relatives of the pancreatic cancer cases. The risk was 7.2% for relatives of cases diagnosed before age 60, and was 12.3% for relatives of patients with multiple primary cancers (all ages). These individuals comprise a high-risk group for pancreatic cancer and might benefit from enhanced surveillance or chemoprevention. Familial site-specific pancreatic cancer appears to be a distinct genetic entity, but contributes only modestly to the total burden of pancreatic cancer.
International Journal of Cancer 02/2002; 97(6):807-10. DOI:10.1002/ijc.10123 · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Susceptibility to pancreatic adenocarcinoma appears to be linked to germ-line mutations in genes causing various familial cancer syndromes. The objectives of this study were to estimate the proportion of unselected pancreatic cancer patients belonging to hereditary cancer syndrome families and to determine the frequency ofp16, BRCA1, BRCA2, hMSH2, and hMLH1 germ-line mutations in patients with a personal or family history of cancer. The study population consisted of 102 patients with histologically verified pancreatic adenocarcinoma, unselected for age, sex, family history, or ethnic origin. Patients completed a family history questionnaire and provided blood for mutation analysis. Three-generation pedigrees were constructed and classified as high risk/familial, intermediate risk/ familial, intermediate risk/nonfamilial, or low risk according to defined criteria. High- and intermediate-risk cases were analyzed for germ-line mutations using a combination of methods. Thirty-eight of 102 (37%) patients were characterized as high or intermediate risk, and the remainder were classified as low risk. Germ-line mutations were identified in five (13%) of these cases [one in p16 (I49S); one in BRCA1 (5382 insC); and three in BRCA2 (6174delT)]. The BRCA1 and BRCA2 mutations were identified in Ashkenazi Jewish patients. Four of the mutation carriers had strong family histories of the syndromes associated with the mutated genes. No mutations were identified in patients in whom the sole risk factor was a family history of pancreatic cancer, and only one mutation was found among patients with early-onset disease. We conclude that known causes of genetic predisposition are an important risk factor in a small proportion of pancreatic cancer patients, especially if associated with a strong family history of syndromes associated with the disease. The lack of detectable germ-line mutations in most high- and intermediate-risk cases suggests that there are probably additional, as yet unidentified genes predisposing to this disease.
Cancer Research 02/2000; 60(2):409-16. · 9.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Immunoscintigraphy of the axilla has potential utility for the diagnostic and prognostic assessment of patients with breast adenocarcinoma. mAb-170H.82 is a murine monoclonal antibody (mAb) derived against synthetic Thomsen-Friedenreich (TF) antigen. Tru-Scint AD, a 99mTc-mAb-170H.82 immunoconjugate, has previously been shown to localize in various human adenocarcinomas. The purpose of this study was to evaluate the accuracy of this immunoconjugate in the pre-operative assessment of axillary lymph nodes in patients with known breast adenocarcinoma. Sixteen patients with documented primary breast cancer were injected intravenously with 1 mg of immunoconjugate (radioactivity 1.8 GBq) and imaged 22-24 hrs post-injection. Both planar and single photon emission computed tomographic (SPECT) images were obtained and reviewed in a blinded fashion. Imaging results were compared with surgical and pathological findings. Seven of 16 patients were found to have histologically positive axillary nodes: 5 of these sites were detected by immunoscintigraphy (sensitivity = 71%). Nine patients had pathologically disease-free axillary nodes: only 1 of these was misidentified as positive by immunoscintigraphy (specificity = 89%). These results suggest that immunoscintigraphy with 99mTc-mAb-170H.82 has promise in the detection of axillary lymph node involvement in patients with breast cancer. Further studies are warranted to define the role of immunoscintigraphy in axillary staging.
Breast Cancer Research and Treatment 09/1997; 45(1):29-37. DOI:10.1023/A:1005878113826 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sixteen patients with colorectal cancer were administered 37-74 MBq (1 mg) of radioiodinated B72.3 monoclonal antibody. Pharmacokinetic analysis was carried out on plasma and urine samples. Elimination from the plasma was biexponential with a mean T1/2 alpha of 3.7 h and T1/2 beta of 62.4 h. The plasma clearance was fit to a two-compartmental model. This was combined with a previously reported model for radioiodine to construct a composite model. There was a good correlation (r = 0.952) between the model-predicted and observed excretion of radioiodine suggesting that the composite model is compatible with the pharmacokinetics of the radiolabelled antibody.
Nuclear Medicine and Biology 02/1993; 20(1):57-64. DOI:10.1016/0969-8051(93)90136-I · 2.41 Impact Factor